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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿(英文)》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要:

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词: epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

H. sinensis mycelium inhibits epithelial-mesenchymal transition by inactivating

Li Lu, Haiyan Zhu, Hailin Wang, Huaping Liang, Yayi Hou, Huan Dou

《医学前沿(英文)》 2021年 第15卷 第2期   页码 313-329 doi: 10.1007/s11684-020-0737-1

摘要: The medical fungus has been used as a Chinese folk health supplement because of its immunomodulatory properties. Our previous studies established the antifibrotic action of mycelium (HSM) in the lung. The epithelial–mesenchymal transition (EMT) is involved in the pathogenesis of idiopathic pulmonary fibrosis. The present study investigates the role of HSM in mediating EMT during the development of pulmonary fibrosis. HSM significantly inhibits bleomycin (BLM)-induced pulmonary fibrosis by blocking the EMT. In addition, the expression levels of midkine are increased in the lungs of the BLM-induced group. Further analysis of the results indicates that the mRNA level of midkine correlated positively with EMT. HSM markedly abrogates the transforming growth factor β-induced EMT-like phenotype and behavior . The activation of midkine related signaling pathway is ameliorated following HSM treatment, whereas this extract also caused an effective attenuation of the induction of EMT (caused by midkine overexpression) . Results further confirm that oral medication of HSM disrupted the midkine pathway . Overall, findings suggest that the midkine pathway and the regulation of the EMT may be considered novel candidate therapeutic targets for the antifibrotic effects caused by HSM.

关键词: epithelial−mesenchymal transition     H. sinensis mycelium     midkine     pulmonary fibrosis    

Lymphatic metastasis is related to the epithelial-mesenchymal transition and expressions of VEGF, MMP

Lihui WANG, Lianhong LI, Shen LV, Shujun FAN, Li ZHAN, Bo WANG, Zhong ZHANG

《医学前沿(英文)》 2009年 第3卷 第2期   页码 164-170 doi: 10.1007/s11684-009-0038-1

摘要: The invasion and metastasis of breast cancer are supposed to involve several stages in which epithelial-mesenchymal transition (EMT) is regarded as the mechanistic basis for the behavior of cancer cells. A series of factors related to EMT are apparently involved in such process. The current study aimed to investigate the contributions of EMT and related factors in lymph node metastasis of breast cancer. The expressions of E-cadherin (E-Cad), N-cadherin (N-Cad), vascular endothelial cell growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and CD34 were examined in 74 cases of breast cancer, including 39 cases with lymph node metastasis and 35 cases without lymph node metastasis by immunohistochemistry. Multivariable Cox proportional hazards model was used to analyze the patients’ prognosis. The expressions of N-Cad, VEGF, MMP-9, and COX-2 in cases with lymph node metastasis were significantly higher than those without lymph node metastasis ( <0.05), while the E-Cad level was inversely related to status of lymph node metastasis ( <0.05). The metastasis rate of lymph node in the cases with EMT (lower E-Cad expression and higher N-Cad expression) was 78.3%, while that without EMT (higher E-Cad expression and lower N-Cad expression) was 11.1%. There was a statistical difference in the expression of COX-2 protein between histological grade I and grade II or III, respectively ( <0.05). In the cases with higher grade, the expression of E-Cad was decreased, while that of N-Cad was increased. Higher microvascular density (MVD) was also found to be significantly associated with lymphatic metastasis ( <0.05), and the cases with higher MVD had shorter survival time. This study indicates that EMT and expressions of VEGF, MMP-9 and COX-2, and MVD value are strongly correlated with lymph node metastasis in breast cancer.

关键词: epithelial-mesenchymal transition     vascular endothelial cell growth factor     matrix metalloproteinase-9     cyclooxygenase-2     higher microvascular density     breast cancer    

Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿(英文)》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要:

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词: diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

《医学前沿(英文)》 2009年 第3卷 第2期   页码 204-210 doi: 10.1007/s11684-009-0039-0

摘要: To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy upon chronic allograft nephropathy (CAN) of rats, male Lewis (LEW, RT11) rats received male Fisher (F344, RT11v1) renal allografts. The recipients were divided into three groups: (1) empty control group; (2) vector control group; (3) gene therapy group. All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation. Morphometric analysis was used to determine the fibrosis of grafts. Immunohistochemistry was used to detect the expression of E-Cadherin, Vimentin, TβR I and the infiltration of CD4 T lymphocyte, CD8 T lymphocyte and ED-1 monocytes. Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 in serum. The grafts in the control group and vector control group showed CAN. There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I. In the gene therapy group, the fibrosis was ameliorated and fewer T lymphocytes and ED-1 monocytes infiltrated in the interstitium. There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats. Compared with the empty control group, the expression of TGF-β1 in the gene therapy group was down-regulated. Adanti-ERK2 gene therapy protects the renal allograft and attenuates graft fibrosis, which may be correlated with a decreased renal tubular epithelial mesenchymal transition, a decreased infiltration of CD4 T lymphocyte, CD8 T lymphocytes and ED-1 monocytes in renal interstitium, and the down-regulated TGF-β1 expression.

关键词: anti-ERK2     renal transplantation     epithelial mesenchymal transition     chronic allograft nephropathy    

Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

《医学前沿(英文)》 2019年 第13卷 第2期   页码 138-151 doi: 10.1007/s11684-018-0627-y

摘要: As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

关键词: mesenchymal stem cell     clinical transition     immune disorders    

Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

《医学前沿(英文)》 2012年 第6卷 第1期   页码 41-47 doi: 10.1007/s11684-012-0175-9

摘要:

Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non-controversial source of early stem cells that can be readily manipulated. As the most common pluripotent cell, bone marrow-derived MSCs display limitations with the progress of stem cell therapy. By contrast, umbilical cord-derived cells, which have plentiful resources, are more accessible. However, several uncertain aspects, such as the effect of donor selection or culture conditions, long-term therapeutic effects, product consistency, and potential tumorigenicity, are the bottleneck in this clinical therapy. MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges. In the current paper, we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies, as well as the achievements of our peers in this field. This paper focuses on the strategies, challenges, and potential of this novel therapy.

关键词: umbilical cord     mesenchymal stem cells     cutaneous regeneration    

Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue

null

《医学前沿(英文)》 2013年 第7卷 第4期   页码 486-491 doi: 10.1007/s11684-013-0287-x

摘要:

The purpose of this study was to compare cell growth characteristics, ciliated cell differentiation, and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue cultures. Human nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture methods. Epithelial cell growth characteristics were observed by inverted phase contrast microscopy. Ciliated cell differentiation was detected by β-tubulin IV and ZO-1 immunocytochemistry. Basal and ATP-stimulated ciliary beat frequency (CBF) was measured using a high-speed digital microscopic imaging system. Both the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition, with both types of cultures comprising ciliated and non-ciliated epithelial cells. Fibroblasts were also frequently found in explant cultures but rarely seen in dissociated tissue cultures. In both culture systems, the highest ciliated cell density appeared at 7th–10th culture day and declined with time, with the lifespan of ciliated cells ranging from 14 to 21 days. Overall, 10% of the cells in explant cultures and 20% of the cells in the dissociated tissue cultures were ciliated. These two cultures demonstrated similar ciliary beat frequency values at baseline (7.78±1.99 Hz and 7.91±2.52 Hz, respectively) and reacted equivalently following stimulation with 100 μM ATP. The results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells, which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.

关键词: ciliated cells     ciliary beat frequency     dissociated tissue culture     explant culture     nasal epithelial cells    

Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 33-39 doi: 10.1007/s11684-011-0114-1

摘要:

Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine.

关键词: mesenchymal stem cells     migration     molecular mechanisms     signaling pathway    

Clinical outcomes and prognostic factors of patients with epithelial ovarian cancer subjected to first-line

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 91-95 doi: 10.1007/s11684-014-0305-7

摘要:

A total of 251 patients with epithelial ovarian cancer (EOC) treated between 2002 and 2008 was retrospectively analyzed to investigate the long-term outcomes and prognostic factors of these patients, particularly those who underwent primary debulking surgery followed by platinum-based chemotherapy. Clinico-pathological parameters, including progression-free survival (PFS) and overall survival (OS), were also analyzed. The median follow-up period from the end of initial treatment to June 2010 was 58 months. The three-year PFS rate was 61.7% for International Federation of Gynecology and Obstetrics (FIGO) I–II, 19.9% for FIGO III–IV, and 33.9% for all stages. By comparison, the five-year PFS rate was 44.6% for FIGO I–II, 17.7% for FIGO III–IV, and 28.3% for all stages. The three-year OS rate was 67.9% for FIGO I–II, 41.7% for FIGO III–IV, and 50.2% for all stages. The five-year OS rate was 52.7% for FIGO I–II, 30.8% for FIGO III–IV, and 39.2% for all stages. Univariate analysis revealed that advanced FIGO stage, serum CA125, and suboptimal debulking were significant factors affecting PFS and OS. In multivariate analysis, PFS was significantly influenced by FIGO stage and suboptimal debulking. However, OS was significantly influenced by advanced FIGO stage only. Our study confirms the efficacy of surgery followed by platinum-based chemotherapy for EOC. FIGO stage is considered as one of the most reliable predictors of the prognosis of patients with EOC.

关键词: ovarian carcinoma     prognostic factors     surgery     chemotherapy     survival    

Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 20-29 doi: 10.1007/s11684-014-0371-x

摘要:

Ischemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique “immunosuppressive and immunoprivilege” property, hUC-MSCs are advised to be an important candidate for allogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.

关键词: cellular therapy     transplantation     human umbilical cord     mesenchymal stem cells     ischemic stroke    

Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like

null

《医学前沿(英文)》 2013年 第7卷 第3期   页码 345-353 doi: 10.1007/s11684-013-0282-2

摘要:

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

关键词: umbilical cord     mesenchymal stem cells     sweat gland     preclinical    

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

《医学前沿(英文)》 2011年 第5卷 第4期   页码 372-378 doi: 10.1007/s11684-011-0164-4

摘要: Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.

关键词: mesenchymal stem cells     differentiation     immunomodulation     regenerative medicine    

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial

《医学前沿(英文)》 2023年 第17卷 第4期   页码 781-795 doi: 10.1007/s11684-023-0986-x

摘要: Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs’ metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

关键词: dry eye disease     glycolytic reprogramming     pyroptosis     inflammation     2-DG    

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 94-100 doi: 10.1007/s11684-011-0116-z

摘要:

Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PD-MSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7?±?18.7 to 34.7?±?13.4 IU (P<0.01), and the C-peptide level was increased from 4.1?±?3.7 ng/mL to 5.6?±?3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

关键词: placenta stem cells     treatment of type 2 diabetes    

标题 作者 时间 类型 操作

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文

H. sinensis mycelium inhibits epithelial-mesenchymal transition by inactivating

Li Lu, Haiyan Zhu, Hailin Wang, Huaping Liang, Yayi Hou, Huan Dou

期刊论文

Lymphatic metastasis is related to the epithelial-mesenchymal transition and expressions of VEGF, MMP

Lihui WANG, Lianhong LI, Shen LV, Shujun FAN, Li ZHAN, Bo WANG, Zhong ZHANG

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

期刊论文

Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

期刊论文

Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

期刊论文

Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue

null

期刊论文

Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction

null

期刊论文

Clinical outcomes and prognostic factors of patients with epithelial ovarian cancer subjected to first-line

null

期刊论文

Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges

null

期刊论文

Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like

null

期刊论文

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

期刊论文

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial

期刊论文

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

null

期刊论文